Enantioselective Total Synthesis of Cotylenin A

A convergent enantio­selective total synthesis of cotylenin A is described. The A-ring fragment, prepared via the catalytic asymmetric intra­molecular cyclopropanation developed in our laboratory, and the C-ring fragment, prepared from a known chiral compound via a modified acyl radical cyclization, were successfully assembled by the Utimoto coupling reaction. The formidable carbocyclic eight-membered ring of cotylenin A was efficiently constructed by a palladium-mediated cyclization. All the hydroxy groups in the scaffold were stereo­selectively introduced, and a modified reducing reagent, Me4NBH­(O2CiPr)3, has been developed. The sugar moiety fragment was prepared via three consecutive carbon–oxygen bond-forming reactions, and the glycosylation was accomplished using Wan’s protocol.